The inhibitory effect of diphenyltin on gap junctional intercellular communication in HEK-293 cells is reduced by thioredoxin reductase 1.
Organotins display high biological activity and are toxic to animals and humans. Besides carcinogenic effects, they have been shown to have highly immunotoxic and/or neurotoxic activity; however, the molecular mechanism of their toxicity is not fully understood. The ability of chemicals to inhibit communication via gap junctions has been associated with their toxicological properties. The aim of this study was to determine whether diphenyltin (DPhT) affects the gap junctional intercellular communication (GJIC) and whether thioredoxin reductase (TrxR1) is involved in the regulation of this process. We found that DPhT inhibits GJIC in HEK-293 cells. The inhibition of GJIC depends on the activation of PKC delta and is associated with the induction of Cx43 phosphorylation at Ser262. Moreover, we found that GJIC inhibited by DPhT in HEK-293 cells is fully re-established as a result of TrxR1 overexpression.
Sroka
Jolanta
J
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Cracow, Gronostajowa 7, Poland. jolanta.sroka@uj.edu.pl
Czyz
Jarosław
J
Wojewoda
Marta
M
Madeja
Zbigniew
Z
D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018031:Connexin 43 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009947:Organotin Compounds / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012694:Serine / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D018031:Connexin 43; D009947:Organotin Compounds; D034741:RNA, Small Interfering; C063612:diphenyltin; D012694:Serine; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D051745:Protein Kinase C-delta